Genetic Variant SLC22A8:c.-16G>A (chr11-63014974-C-T) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_004254.4(SLC22A8):c.-16G>A variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0423 in 1,530,816 control chromosomes in the GnomAD database, including 2,777 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.053 ( 420 hom., cov: 33)

Exomes 𝑓: 0.041 ( 2357 hom. )

Consequence

SLC22A8
NM_004254.4 5_prime_UTR

Scores

Splicing: ADA: 0.00009464

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -4.22

Variant links:

Genes affected

SLC22A8 (HGNC:10972): (solute carrier family 22 member 8) This gene encodes a protein involved in the sodium-independent transport and excretion of organic anions, some of which are potentially toxic. The encoded protein is an integral membrane protein and appears to be localized to the basolateral membrane of the kidney. Multiple alternatively spliced transcript variants that encode different protein isoforms have been described for this gene. [provided by RefSeq, May 2010]

SLC22A8 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.82).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.234 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	MANE	Protein	UniProt
SLC22A8	NM_004254.4 link	c.-16G>A	5_prime_UTR_variant	Exon 2 of 11	ENST00000336232.7	NP_004245.2	Q8TCC7-1
SLC22A8	NM_001184732.2 link	c.-4-12G>A	intron_variant	Intron 1 of 10		NP_001171661.1	Q8TCC7-1B2R807
SLC22A8	NM_001184733.2 link	c.-25-264G>A	intron_variant	Intron 1 of 10		NP_001171662.1	Q8TCC7-4
SLC22A8	NM_001184736.2 link	c.-37+755G>A	intron_variant	Intron 1 of 9		NP_001171665.1	Q8TCC7-5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SLC22A8	ENST00000336232.7 link	c.-16G>A		5_prime_UTR_variant	Exon 2 of 11	1	NM_004254.4	ENSP00000337335.2		Q8TCC7-1

Frequencies

GnomAD3 genomes

AF:

0.0533

AC:

8104

AN:

152096

Hom.:

422

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0561

Gnomad AMI

AF:

0.0110

Gnomad AMR

AF:

0.103

Gnomad ASJ

AF:

0.0176

Gnomad EAS

AF:

0.246

Gnomad SAS

AF:

0.0527

Gnomad FIN

AF:

0.0388

Gnomad MID

AF:

0.0127

Gnomad NFE

AF:

0.0306

Gnomad OTH

AF:

0.0511

GnomAD3 exomes

AF:

0.0765

AC:

14660

AN:

191522

Hom.:

1153

AF XY:

0.0703

AC XY:

7144

AN XY:

101554

show subpopulations

Gnomad AFR exome

AF:

0.0569

Gnomad AMR exome

AF:

0.177

Gnomad ASJ exome

AF:

0.0240

Gnomad EAS exome

AF:

0.259

Gnomad SAS exome

AF:

0.0532

Gnomad FIN exome

AF:

0.0455

Gnomad NFE exome

AF:

0.0317

Gnomad OTH exome

AF:

0.0525

GnomAD4 exome

AF:

0.0411

AC:

56626

AN:

1378602

Hom.:

2357

Cov.:

AF XY:

0.0407

AC XY:

27461

AN XY:

675438

show subpopulations

Gnomad4 AFR exome

AF:

0.0556

Gnomad4 AMR exome

AF:

0.161

Gnomad4 ASJ exome

AF:

0.0201

Gnomad4 EAS exome

AF:

0.238

Gnomad4 SAS exome

AF:

0.0499

Gnomad4 FIN exome

AF:

0.0418

Gnomad4 NFE exome

AF:

0.0292

Gnomad4 OTH exome

AF:

0.0459

GnomAD4 genome

AF:

0.0532

AC:

8104

AN:

152214

Hom.:

420

Cov.:

AF XY:

0.0547

AC XY:

4067

AN XY:

74408

show subpopulations

Gnomad4 AFR

AF:

0.0560

Gnomad4 AMR

AF:

0.103

Gnomad4 ASJ

AF:

0.0176

Gnomad4 EAS

AF:

0.246

Gnomad4 SAS

AF:

0.0532

Gnomad4 FIN

AF:

0.0388

Gnomad4 NFE

AF:

0.0306

Gnomad4 OTH

AF:

0.0501

Alfa

AF:

0.0336

Hom.:

291

Bravo

AF:

0.0602

Asia WGS

AF:

0.154

AC:

533

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.82

CADD

Benign

7.6

DANN

Benign

0.82

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.000095

dbscSNV1_RF

Benign

0.0040

SpliceAI score (max)

0.070

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

LitVar

Other links and lift over